Neurochemical Research

, Volume 37, Issue 9, pp 2025–2032

Effect of Trehalose on PC12 Cells Overexpressing Wild-Type or A53T Mutant α-synuclein

  • Dan-Mei Lan
  • Feng-Tao Liu
  • Jian Zhao
  • Yan Chen
  • Jian-Jun Wu
  • Zheng-Tong Ding
  • Zhen-Yu Yue
  • Hui-Min Ren
  • Yu-Ping Jiang
  • Jian Wang
Original Paper

DOI: 10.1007/s11064-012-0823-0

Cite this article as:
Lan, DM., Liu, FT., Zhao, J. et al. Neurochem Res (2012) 37: 2025. doi:10.1007/s11064-012-0823-0

Abstract

Accumulation of α-synuclein (α-Syn) is a common pathology for both familiar and sporadic Parkinson’s disease (PD), enhancing its clearance might be a promising strategy for treating PD. To assess the potential of trehalose in this regard, we investigated its effect on the PC12 cells overexpressing wild type (WT) or A53T mutant α-Syn and the implicated pathway it might mediated. We observed that trehalose promoted the clearance of A53T α-Syn but not WT α-Syn in PC12 cells, and confirmed the increased LC3 and Lysotracker RED positive autolysosomes by using lysotracker and LC3 staining, the enhanced expression of LC3-II in Western blot, and more autophagosomes under Transmission Electron Microscope in a dose dependent manner after the trehalose treatment. The activation of autophagy can be alleviated by applying macroautophagy inhibitor 3-methyladenine (3-MA). In addition, degradation of A53T and WT α-Syn was blocked after Ubiquitin Proteasome System (UPS) inhibitor (MG132) was applied in those PC12 cells overexpressing A53T or WT α-Syn, suggesting that A53T α-Syn could be degraded by both UPS and macroautophagy. But the effect of trehalose on A53T α-Syn is mainly mediated through the macroautophagy pathway, which is not a dominant way for WT α-Syn clearance. Further in vivo research will be needed to verify the effectiveness of trehalose in treating PD.

Keywords

Trehalose α-synuclein Parkinson’s disease Autophagy Macroautophagy Proteasome inhibitor 

Abbreviations

α-Syn

α-synuclein

PD

Parkinson’s disease

WT

Wild type

3-MA

3-methyladenine

UPS

Ubiquitin Proteasome System

ALS

Autophagy Lysosome System

TEM

Transmission electron microscope

DMSO

Dimethyl sulfoxide

MTT

3-(4,5-dimethylthiazol-2-yl)-2,5-dipheyltetrazolium Bromide assay

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Dan-Mei Lan
    • 1
    • 2
    • 4
  • Feng-Tao Liu
    • 1
    • 2
  • Jian Zhao
    • 1
    • 2
  • Yan Chen
    • 1
    • 2
  • Jian-Jun Wu
    • 1
    • 2
  • Zheng-Tong Ding
    • 1
    • 2
  • Zhen-Yu Yue
    • 3
  • Hui-Min Ren
    • 1
    • 2
  • Yu-Ping Jiang
    • 1
    • 2
  • Jian Wang
    • 1
    • 2
  1. 1.Department of Neurology, Huashan Hospital, Shanghai Medical CollegeFudan UniversityShanghaiChina
  2. 2.Department and Institute of Neurology, Shanghai Medical CollegeFudan UniversityShanghaiChina
  3. 3.Department of Neurology and NeuroscienceMount Sinai School of MedicineNew YorkUSA
  4. 4.Department of NeurologyShanghai Changzheng Hospital, Second Military Medical UniversityShanghaiChina

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